1. Field of the Invention
The present invention relates to a method of manufacturing a detection device of a semiconductor apparatus, and more particularly, to a method of manufacturing a deoxyribonucleic acid (DNA) chip.
2. Description of the Related Art
Each of human cells has 23 pairs of chromosomes which includes a lot of genes that can make about 100,000 proteins. All human cells are not able to produce about 100,000 proteins, rather, only some of the genes produce necessary proteins. Assuming that about 10,000 genes are involved in producing proteins in cells, a method of detecting such genes will be described below.
DNA information responsible for producing proteins (e.g., three base sequences such as ATT and CGA) is transferred to ribonucleic acid (RNA). RNA including the DNA information is transported to a ribosome allocated outside a nucleus and synthesizes proteins at the ribosome. Therefore, enormous amounts of DNA information can be detected by sorting RNAs synthesized at cells and decoding base sequences of the RNAs. However, with this method, it would take about a day to find out the genetic structure for synthesizing one protein. Thus, it would take about 10,000 days to find out all the genetic structures.
A recently developed DNA chip greatly shortens the time taken to find out a vast amount of cellular genetic information. The DNA chip includes several hundred thousand DNA probes, and enables researchers to simultaneously monitor the activity of several thousand genes and detect defects. Also, a genetic expression activity of producing proteins in response to the activation of a gene can be estimated using the DNA chip.
The basic principle of the DNA chip is the use of DNA having a single stranded helical structure. The cellular RNA structure is changed into a DNA structure by treating the unstable cellular RNA structure to obtain a stable experimental material containing the same genetic information. Since RNA has a single stranded helical structure, the DNA obtained from the RNA in this way has a single stranded helical structure instead of a double stranded helical structure.
For a detection method of a specific gene using the DNA chip, different DNA probes are prepared within about 100,000 wells of the DNA chip. Each of the DNA probes has a single stranded helical structure. When about 10,000 cellular genes (i.e. DNA) to be detected are injected into the wells of the DNA chip, hybridization between the DNA probes and the injected cellular DNA is initiated at about 10,000 wells of the DNA chip. Hence, assuming that base sequences of about 100,000 genes are all discovered, the 10,000 hybridized genes can be identified from the DNA chip, thereby obtaining the desired genetic information. Knowing the base sequences of DNA makes it possible to identify which amino acids are produced, and thus about 10,000 cellular proteins can be identified using the DNA chip.
Although the DNA chip can be manufactured by various methods, a method of attaching previously synthesized DNA probes to a solid substrate and a method of stacking DNA probes on a solid substrate have recently been employed.
In the conventional DNA chip manufacturing methods, DNA probes are synthesized by photolithography, as commonly used in semiconductor device fabrication.
In this method, an organic layer to be hybridized with bases of DNA probes, for instance, a GAPS layer, exists on a glass substrate. A photoresist layer, which is used in a typical semiconductor fabrication process, is first formed on the organic layer for the purpose of attaching a specific DNA probe to a selected portion of the organic layer. Using a photo-mask exposing a portion of the photoresist layer which covers the selected portion of the organic layer, the exposed portion of the photoresist layer is exposed to light. A developing solution is used to develop the photoresist layer, and the photo-exposed portion of the photoresist layer formed on the selected portion of the organic layer is removed. The resulting structure where the photoresist layer remains on the organic layer except for the selected portion is immersed in a solution including a specific base to be hybridized with the selected portion of the organic layer, and then cleaned. As a result, the specific base (i.e. the DNA probe) is attached to the selected portion of the organic layer, which is exposed by the previous developing process. These sequential operations are performed at other regions of the organic layer.
Compared with conventionally employed methods such as Southern blot, Northern blot, mutant detection, and DNA sequencing, the DNA chip manufactured as above can detect more genes with less specimens within a shorter time. However, the photoresist layer adheres well to the organic layer and the DNA probe. Thus, during the developing process, the photoresist layer may not be completely removed from the organic layer or the DNA probe, and may partially remain on the organic layer or the DNA probe, degrading the activation of the organic layer.